Leukotriene is a lipid mediator produced from arachidonic acid by 5-lipoxygenase and involved in inflammation and contraction of airway muscle and decrease/accumulation of the fluid amount in lung. Leukotriene C4, D4, and E4, which contain cysteine in their molecules, are called cysteinyl leukotriene, and cysteinyl leukotriene 1 (hereinafter referred to as “CysLT1”) receptor and cysteinyl leukotriene 2 (hereinafter referred to as “CysLT2”) receptor are known as a receptor thereof. CysLT 1 receptors and CysLT2 receptors, both of which are expressed in mastocytes, eosinophils, and endothelial cells, induce inflammation in endothelial cells under the stimulus of cysteinyl leukotriene, provide stimulation of chemokine production by mast cells, and are responsible for causing bronchial asthma and inflammatory disease.
Montelukast is an orally-active leukotriene receptor antagonist that selectively inhibits CysLT1 receptors. Sodium salts of montelukast (hereinafter referred to as “montelukast sodium”) have been used as a useful therapeutic agent for respiratory disease, asthma, and allergic rhinitis. However, montelukast sodium has very high hygroscopicity, and it has been reported that Singulair (registered trademark) tablets and Kipres (registered trademark) tablets, which are commercially available as a pharmaceutical, have a problem in that they cause delayed disintegration and delayed dissolution due to moisture absorption upon storage for 4 weeks under conditions of 25° C. and a relative humidity of 85% (hereinafter referred to as “85% RH”) ( “Information on the stability of tablets and capsules in unpacked condition,” (6th revised edition), Nishioka et al., Iyaku (Medicine and Drug) Journal Co., Ltd., 2009, p. 237).
As a method of improving the hygroscopicity of montelukast sodium, using montelukast sodium after converting it into free acid has been reported (JP 2007-508271). However, a method of improving the hygroscopicity of montelukast sodium using a formulation approach has not been reported yet.
In general, as a method of improving hygroscopic stability of a solid preparation, sugar-coating of a solid preparation and film-coating of a solid preparation with a macromolecular substance have been put to practical use. For the latter film-coating, an aminoalkyl methacrylate copolymer E (Eudragit EPO (registered trademark); Degussa) is known as a macromolecular substance that exhibits moisture barrier properties, and a film coating agent having an improved moisture barrier performance by adding stearic acid to an aminoalkyl methacrylate copolymer E (JP 2004-518750) have been developed.
Even in the case where a solid preparation is not coated directly with a film, there is the case where hygroscopic stability is secured by packaging with packaging materials having high water vapor barrier properties. Examples of such a case include the case where a solid preparation is indirectly protected from moisture by placing the solid preparation in a PTP (press through pack) sheet laminated with polyvinylidene chloride and sealing the sheet.
On the other hand, from the standpoint of preventing forgetting to take prescribed drugs or taking a wrong dose, one-dose packages have been widely used at clinical sites and dispensing pharmacies recently. One-dose packages are provided to patients such that a pharmacist takes out a plurality of solid preparations to be taken in one dose from a packaging material such as a PTP sheet and puts them in one package for each patient. In addition, in western countries, patients often subdivide a pharmaceutical taken out from a package such as a PTP sheet for storage in a pill case or the like, and therefore methods for improving the water vapor barrier properties of a solid preparation itself have been demanded.
However, in one-dose packaging, since each solid preparation will be stored for a long period of time in an automatic packing machine in a naked state as taken out in advance from a packaging material such as a PTP sheet, the protective effect of the packaging material against humidity wears off, and particularly for a solid preparation containing montelukast sodium which has high hygroscopicity as an active ingredient, it is extremely difficult at present to formulate in a one-dose package because of being susceptible to humidity during storage. In other words, patients who receive a preparation containing montelukast sodium as an active ingredient have not gained the advantage of one-dose package that it improves drug compliance to enhance a therapeutic effect and, therefore, there is a need to develop, using a formulation approach, a preparation adaptable to one-dose package containing montelukast sodium as an active ingredient.
Thus, it could be helpful to provide a montelukast-containing coated solid preparation that can be applied to one-dose package, wherein the humidity stability of montelukast or a pharmacologically acceptable salt thereof contained therein is maintained even when the preparation is unpacked.